The iron metabolism of cardiac muscle (and of other muscles) is poorly understood. The project proposed focuses on two potentially unique aspects of cardiac iron metabolism, (1) the pculiar ferritins present in heart muscle cells, and (2) the pathway(s) by which iron enters and leaves these cells, especially the intracellular, transit iron pools. With regard to the ferritins, we have shown that heart cells contain a larger form of ferritin, as well as one or more small species, not bound in non-muscle tissues. Our objective is (a) to relate these structural differences to differences in subunit composition/gene expression, by "profiling" subunit composition with HPLC; (b) to investigate the possibility that the small ferritin forms are on their way to the plasma (to be part of serum ferritin) and/or are precursors of the larger ferritins in these cells. As concerns transit iron pools, we have demonstrated the association of significant and consistent portions of tissue and cellular iron with up to 3 components of low molecular weight, some of which may be involved in the steps leading from transferrin to known iron proteins and ferritins, and/or the re-release of iron from cells to the plasma or interstitial fluid. The goal is to chracterize the iron components and their roles in iron transport for the heart in comparison with that of other cell types, in vivo and in vitro in cell culture. It is expected that these studies will give us insights into the peculiar iron needs of heart muscle cells in the normal state and in their response to trauma.